- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg., capecitabine / Generic mfg.
Treatment and survival of patients with de novo metastatic colorectal cancer (mCRC) rested for KRAS, NRAS or BRAF mutations (Section 32) - Mar 9, 2022 - Abstract #AACR2022AACR_5850;
However, contrary to survival data from clinical trials, which exclude vulnerable populations, patients treated with VEGFi did not experience survival benefits, highlighting the importance of examining survival outcomes in routine clinical care. In patients with RAS WT tumors, treatment with EGFRi was associated with improved survival compared with those treated with VEGFi.
- |||||||||| mitazalimab (ADC-1013) / Alligator Biosci
Mitazalimab, a potent CD40 agonist in combination with chemotherapy redirects and activates tumor infiltrating myeloid cells (Section 34) - Mar 9, 2022 - Abstract #AACR2022AACR_5833;
P1, P1b/2
By converting the MB49 tumor cell line resistant to FOLFIRINOX treatment, we could further demonstrate that the combination of mitazalimab and FOLFIRINOX induced a strong anti-tumor activity also in a chemoresistant variant of the MB49 cell line.In conclusion, mitazalimab synergizes effectively with chemotherapy, leading to induction of long-term survival in a preclinical tumor model by reducing immunosuppressive M2 macrophages and improving T cell responses intratumorally. These preclinical data, together with the clinical data of mitazalimab from the phase 1 study (NCT02829099), where mitazalimab was well tolerated up to 1200 μg/kg with a manageable safety profile, support the ongoing clinical phase 2 study OPTIMIZE-1 (NCT04888312) of mitazalimab in combination with chemotherapy in pancreatic cancer.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg.
The identification and characterization of FOLFOX chemotherapy resistant cell lineages in colorectal cancer organoids (Section 9) - Mar 9, 2022 - Abstract #AACR2022AACR_5677;
However, the longtime gold-standard FOLFOX chemotherapy regimen, consisting of 5-FU and Oxaliplatin, results in only 70% survival rates in Stage 3 CRC patients, worse in Stage 4...By identifying these HPP cell populations, we then discover drugs that prevent the development of drug-resistant subpopulations. In the long term, we use our tumor heterogeneity profile to develop models that predict the responsiveness of tumors, including their drug-resistant HPP subpopulations, to well-documented and clinically used oncology drugs, streamlining treatment and improving survival outcomes.
- |||||||||| 5-fluorouracil / Generic mfg., oxaliplatin / Generic mfg., leucovorin calcium / Generic mfg.
Epigenetic mechanisms involved in acquired resistance to combined chemotherapies in digestive cancer cells (Section 3) - Mar 9, 2022 - Abstract #AACR2022AACR_5560;
We have shown that PRDM1 and KDM4B are expressed heterogeneously in cancer cell populations and overexpressed during specific time frames along the acquisition of resistance to oxaliplatin-based combined therapies both in colon and pancreatic cancer cells...Altogether, our data indicate that specific expression of chromatin modifier enzymes, most likely acting as epigenetic complexes, are key milestones of acquired resistance to conventional therapies. This work will pave the way for considering epienzyme-epienzyme interactions as potent drug targets that could circumvent cancer cell aggressiveness.
- |||||||||| Effect of folfirinox with an ATR inhibitor on pancreatic tumor cells and its microenvironment (Section 22) - Mar 9, 2022 - Abstract #AACR2022AACR_4655;
It has showed a significant increase of the overall survival inpatients compared to gemcitabine, but associated with more toxicity and still limited efficiency...In vivo, the association inhibits significantly the tumor growth compared to each treatment alone and no toxicity was observed. Now, validation of this polychemotherapy in vivo using co-culture models in immunodeficient and immunocompetent mice are crucial to confirm the therapeutic potential of this new treatment for PDAC.
- |||||||||| 5-fluorouracil / Generic mfg.
p53 suppresses 5 fluorouracil induced PDL1 upregulation in colorectal cancer cells (Section 24) - Mar 9, 2022 - Abstract #AACR2022AACR_4044;
This work adds significantly to our understanding of how p53 status impacts response to 5FU, in CRC cells with important implications for clinical response and patient stratification. Additionally, this study suggests the rational combination of 5FU with immune checkpoint inhibitors for the treatment of p53 mutant CRC.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg., gemcitabine / Generic mfg.
MYC drives phenotypic heterogeneity, metastasis, and therapy resistance in pancreatic ductal adenocarcinoma (Section 8) - Mar 9, 2022 - Abstract #AACR2022AACR_3516;
Human PDAC is often resistant to standard of care therapies such as gemcitabine and FOLFIRINOX...Together, this work investigates the role of deregulated MYC expression in metastatic behavior, immune phenotypes, and therapeutic response in murine PDAC. It also provides both spontaneous and orthotopic mouse models of PDAC that recapitulate the heterogeneous and highly metastatic nature of the human disease, allowing for important therapeutic testing opportunities.
- |||||||||| EC359 / Evestra
Antiproliferative activity of EC359, an inhibitor of leukemia inhibitory factor receptor (LIF-R), singly and in combination with chemotherapy drugs against pancreatic cancer cell lines (Section 21) - Mar 9, 2022 - Abstract #AACR2022AACR_3250;
Although combination chemotherapy treatments such as FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan), gem-abraxane (gemcitabine and nab-paclitaxel) and GTX (gemcitabine, docetaxel and capecitabine) have improved survival of pancreatic cancer patients incrementally, 5-year-survival for this disease remains dismal...EC359 was also synergistic with IBR120 (a novel small molecule inhibitor of RAD51) against PANC-1 cells...The nanomolar activity of EC359 against pancreatic cancer cell lines makes it a good candidate for potential treatment of this generally refractory disease. The synergistic interaction of EC359 with standard-of-care drugs provides an opportunity for increasing the therapeutic index for these agents, and ultimately improving clinical outcomes for pancreatic cancer and other cancers against which EC359 is currently in clinical trial.
- |||||||||| Identification of aneuploidy biomarkers associated with response to first-line treatment of metastatic pancreatic cancer (Section 30) - Mar 9, 2022 - Abstract #AACR2022AACR_3163;
Background: NCCN guidelines for first-line treatment of patients with metastatic pancreatic cancer includes either FOLFIRINOX or gemcitabine plus paclitaxel; however, these two treatment regimens have not been compared in a randomized clinical trial... In metastatic pancreatic cancer, we found different chromosome arm-level aneuploidies were associated with survival for FOLF and G+P regimens which suggests an aneuploidy-based risk score may have utility in choosing first-line treatment.
- |||||||||| Prognostic and predictive drug-induced gene signatures for colorectal cancer patients personalized based on p53 status and treatment with FOLFOX, 5-FU, oxaliplatin, or irinotecan (Section 30) - Mar 9, 2022 - Abstract #AACR2022AACR_3151;
CRC is often treated with chemotherapeutic agents 5-fluorouracil, irinotecan, and oxaliplatin, but predictive biomarkers are limited...Accompanying data on drug regulation of predictive genes provides valuable information in evaluating clinical impact of pan-drug or drug-specific mechanisms. Future directions include associations with clinically relevant features (microsatellite instability, tumor sidedness, and age), establishment of multi-gene signatures to improve clinical utility, and evaluation of other regimens including FOLFIRI and FOLFOXIRI.
- |||||||||| Abraxane (albumin-bound paclitaxel) / BMS, Otsuka
Identification of the PDAC immunogenic subtype using deep learning with multi-scaled digital H&E images (Section 28) - Mar 9, 2022 - Abstract #AACR2022AACR_2504;
This study presents a deep learning 2-step model approach using tumor H&E images to identify PDAC immunogenic subtype, with improved prognostic potential to that identified by RNA profiling, suggesting possible application in clinical settings for patient stratification. Future work will expand the model to larger independent cohorts.
- |||||||||| Enrollment closed, Trial completion date, Trial primary completion date, Metastases: AFEMA: Study to Assess the Efficacy and Safety of Treatment With FOLFIRI-aflibercept Compared to Initial Treatment With FOLFIRI-aflibercept (for 6 Cycles) Followed by Maintenance With 5FU-aflibercept, in an Elderly Population With mCRC After Failure of an Oxaliplatin-based Regimen (clinicaltrials.gov) - Mar 9, 2022
P2, N=170, Active, not recruiting,
Trial completion date: Dec 2021 --> Feb 2026 | Trial primary completion date: Dec 2021 --> Feb 2026 Recruiting --> Active, not recruiting | Trial completion date: Oct 2021 --> Oct 2022 | Trial primary completion date: Oct 2021 --> Oct 2022
- |||||||||| oxaliplatin / Generic mfg.
Trial completion, Enrollment change, Trial completion date: Lidocaine for Oxaliplatin-induced Neuropathy (clinicaltrials.gov) - Mar 9, 2022
P1/2, N=26, Completed,
Recruiting --> Active, not recruiting | Trial completion date: Oct 2021 --> Oct 2022 | Trial primary completion date: Oct 2021 --> Oct 2022 Active, not recruiting --> Completed | N=38 --> 26 | Trial completion date: Dec 2021 --> Apr 2021
- |||||||||| Avastin (bevacizumab) / Roche, Lynparza (olaparib) / Merck (MSD), AstraZeneca
P3 data, Journal: Olaparib with or without bevacizumab or bevacizumab and 5-fluorouracil in advanced colorectal cancer: Phase III LYNK-003. (Pubmed Central) - Mar 8, 2022
P3
Oxaliplatin-based chemotherapy with a regimen such as FOLFOX with or without targeted therapy is a standard of care option for advanced colorectal cancer; however, long-term exposure to oxaliplatin is associated with cumulative toxicity...The primary end point is progression-free survival by independent central review; secondary end points include overall survival, objective response, duration of response and safety. Clinical trial registration: NCT04456699.
- |||||||||| Avastin (bevacizumab) / Roche, Herceptin (trastuzumab) / Roche, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Real-World Utilization Patterns of Oncology Biosimilar Monoclonal Antibodies and Their Corresponding Reference Products (In-person & Virtual) - Mar 8, 2022 - Abstract #ISPOR2022ISPOR_1644;
The objective of this study was to describe real-world treatment pattens of rituximab-pvvr, trastuzumab-qyyp, and bevacizumab-bvzr and their associated reference biologics...Both originator and biosimilar products were used along with specific drug regimens for NHL (CHOP, CVP, DHAP), BC (docetaxel+carboplatin+pertuzumab, docetaxel+carboplatin, pertuzumab+paclitaxel/docetaxel), and CRC (FOLFOX, CAPOX, FOLFIRI, FOLFOXIRI). Biosimilar-mAb products are being utilized in a manner similar to their reference biologic-mAbs in real-world clinical settings.
- |||||||||| Avastin (bevacizumab) / Roche
Patterns of Provider Imaging Practices and Associated Outcomes of Advanced Colorectal Cancer (In-person & Virtual) - Mar 8, 2022 - Abstract #ISPOR2022ISPOR_760;
METHODS : Using Optum’s de-identified Clinformatics® Data Mart Database (2008-2016), we identified patients with CRC, and selected treatment-naïve patients who received combination chemotherapies, fluoropyrimidines with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI), or capecitabine with either oxaliplatin (XELOX) or irinotecan (XELIRI), combined with bevacizumab...CONCLUSION : A more intensive follow-up schedule was associated with greater likelihood of treatment switch, yet it was not associated with the better survival outcome. Further studies with longer follow up period of CRC patients are required in the future.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS
Cost-Effectiveness Analysis of Nivolumab Plus Chemotherapy Vs Chemotherapy in Patients with Advanced Gastric Cancer in Japan (Virtual) - Mar 8, 2022 - Abstract #ISPOR2022ISPOR_379;
OBJECTIVES: This study aimed to evaluate the cost-effectiveness of combination therapy of nivolumab plus chemotherapy (FOLFOX or XELOX) (Niv+Chemo) comparing with chemotherapy alone for patients with advanced gastric cancer (AGC) in Japan from the perspective of Japanese payer... The combination therapy of nivolumab plus chemotherapy as first-line therapy would not be cost-effective under a willingness-to-pay threshold of USD75,000/QALY.
- |||||||||| leucovorin calcium / Generic mfg.
Variants in PNPLA8 are Associated with Developmental Epileptic Encephalopathy and Cerebellar Atrophy. (Poster Hall) - Mar 6, 2022 - Abstract #AAN2022AAN_4019;
The EEG showed burst suppression pattern and multifocal seizures refractory to multiple anti-seizure medications and vitamins/cofactors including pyridoxine, folinic acid, pyridoxal-5-phosphate, and biotin... Likely pathogenic variants in the PNPLA8 gene appear to be causative of the developmental epileptic encephalopathy that encompasses both myoclonic epilepsy of infancy and Ohtahara Syndrome.
- |||||||||| methotrexate / Generic mfg.
Methotrexate Induced CNS Neurotoxicity: Is It Always Leukoencephalopathy? (Poster Hall) - Mar 6, 2022 - Abstract #AAN2022AAN_3355;
Clinical features often include a subacute encephalopathy with a fluctuating course followed by frequent improvement of symptoms. While MTX neurotoxicity commonly affects the white matter, symmetrical involvement of the basal ganglia may also occur.
- |||||||||| oxaliplatin / Generic mfg., cisplatin / Generic mfg., pregabalin / Generic mfg.
Isolated Oxaliplatin Induced Lhermitte's sign in Rectal Cancer (Poster Hall) - Mar 6, 2022 - Abstract #AAN2022AAN_3354;
To best of our knowledge, only 13 cases of Oxaliplatin induced Lhermitte’s sign has been reported in patients with diagnosis of colorectal cancer in English literature. Most of these cases were previously diagnosed with oxaliplatin induced dose-dependent sensory polyneuropathy upon presentation of Lhermitte’s sign.
- |||||||||| Abraxane (albumin-bound paclitaxel) / BMS, Otsuka
Review, Journal: Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancer: Chemotherapy or Chemoradiotherapy? (Pubmed Central) - Mar 4, 2022
Radiotherapy appears to play an important role in mediating locoregional effects. Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg.
Trial completion date, Metastases: FOLFOX-A For Locally Advanced Pancreatic Cancer: A Phase II Brown University Oncology Research Group Trial (clinicaltrials.gov) - Mar 4, 2022
P2, N=28, Active, not recruiting,
Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC. Trial completion date: Dec 2021 --> Dec 2024
- |||||||||| GC-1118A / GC Biopharma
Trial completion, Trial completion date, Combination therapy, Metastases: A Study to Assess Safety, Efficacy, Immunogenicity, PK of GC1118 With Combination Chemotherapy (clinicaltrials.gov) - Mar 3, 2022
P1b/2a, N=53, Completed,
However, prospective randomized data about the superiority to gemcitabine monotherapy are needed. Active, not recruiting --> Completed | Trial completion date: Jun 2021 --> Jan 2022
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